The objective of the proposed research is to study systematically factors involved in the pathogensis, course, prevention and treatment of experimental infective endocarditis in the rabbit. Host factors to be examined will include the relationship of preexisting humoral and cellular immunity, circulating immune complexes, thrombus formation, and prosthetic material to the induction, course, and response to treatment of the infection. Microbiological factors that will be studied include an analysis of surface components, extracellular products and antibiotic resistance and their relationship to adherence to heart valves, virulence and response to therapy. The method to be employed involves the production of sterile vegetations on the endocardium of rabbits by the introduction of a sterile polyethylene catheter. These vegetations regulary become infected when bacteria are administered intravenously. Major emphasis will be placed on the immunological and pathogenetic aspects that may be applicable to the understanding, prevention and management of human bacterial endocarditis.